Despite lack of evidence, the practice of routine prefeed gastric residue aspiration before the next feed is common. Recent studies suggest that this practice might be even harmful. Therefore, we aimed to evaluate the effect of avoiding routine prefeed gastric residue aspiration as compared to routine aspiration, on various clinical outcomes in preterm infants. We searched five different electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane Library) until March 8, 2021. Only randomized controlled trials comparing the practice of routine prefeed gastric aspiration with no routine aspiration in preterm infants were considered eligible. The random-effects meta-analysis was done using RevMan 5.3 software. Of the 894 unique records identified by our search, we included 6 studies (451 participants) in the review. There was no significant difference in the incidence of necrotizing enterocolitis (RR 0.80; 95% CI 0.31 to 2.08; 421 participants in 5 trials). Avoiding routine prefeed aspiration was associated with achieving full enteral feeds earlier (MD – 3.19 days, 95% CI – 4.22 to – 2.16), shorter duration of hospitalization (MD – 5.32 days; 95% CI – 10.25 to – 0.38), and lower incidence of late-onset sepsis (RR 0.77; 95% CI 0.60 to 0.99). Time to regain birth weight, days of total parenteral nutrition or central venous line usage, culture-positive sepsis, and all-cause mortality did not differ between the two groups.Conclusion: In the absence of other signs of feed intolerance, routine prefeed gastric residue aspiration should be avoided in preterm infants.Prospero registration number: CRD42020197657 What is Known: • Though, routine prefeed aspiration before next feed is a common practice in preterm gavage-fed infants. • Recent study suggests that the omission of routine gastric residual evaluation led to improved weight gain and earlier hospital discharge. What is New: • Low- to moderate-quality evidence suggest that avoiding routine prefeed gastric residue monitoring helps in the reduction of late-onset sepsis, achieving full enteral feeds earlier, and earlier discharge from the hospital. • Abandoning the practice of routine prefeed aspiration in absence of other signs of feed intolerance in preterm low birthweight neonates is safe.